OPEN-ACCESS PEER-REVIEWED
RESEARCH ARTICLE
Ravikumar Vejendla, Sri Hari Galla, Sivanna Chithanna
1Department of Pharmaceutical Analysis, St.Mary’s Pharmacy College, Deshmukhi, Hyderabad.
2Medicinal Chemistry Department, University of Louisville, 505 South Hancock Street, Louisville, KY 40202, USA
3Dr. Sudipta Narayan Roy, BHMS (Cal), FWT (Cal), SMEP (IIM,A), DipHomoeo (Germany), DipOnco (UK), Managing Director & Group CEO Powell Laboratories (P) Limited GN 28, Sector- V, Salt Lake City, Kolkata – 700091, West Bengal, India.
Journal of Applied Bioanalysis. Vol. 10.
DOI: https://doi.org/10.53555/jab.v10i2.159 | (ISSN 2405-710X)
Abstract
Background: authors want to define the procedure for LC-ESI-MS/MS, a technique utilized in bio-analytical research to establish a simple technique for determining the level of Niraparib in K3EDTA plasma from human beings, is a combination of liquid chromatography, electro spray ionization and mass spectro-photometry. Niraparib in plasma samples has been measured using a sensitive and efficient technique.
Materials and methods: Chromatographic elution was done by using 10mM Ammonium acetate pH-5.0 (A) : acetonitrile (B) in the ratio of 10:90v/v as mobile phase having flow rate of 1.0 milli-liter per minute, Gemini 5µ C18150 x 4.6 mm column. 70% division of flow was used for chromatographic separation of Niraparib with an ISTD as Niraparib-D5.
Results: System Suitability: Area ratio < 2.06%, ISTD RT, and analyte RT% CV ≤ 2.06%. System performance: internal standard residual ≤ 1.07, analyte carryover < 6045, signal to noise ratio ≥ 270.0. Over LOQ & LOQQC 0.0005 µg/ml, LQC 0.00134 µg/mL, MQC 0.02 µg/mL and HQC 0.04 µg/mL, this approach is verified, ULOQ 0.05 µg/mL, and linear concentration range of 0.0005 µg/mL to 0.05 µg/mL with a correlation coefficient (r2) of ≥ 0.9997. Stability investigations indicated that the developed conduct was suitable for use with K3EDTA plasma samples when it was validated.
Summary: The LC-MS/MS technique that was created to quantify the amount of Niraparib in the biological matrix worked well for routine blood sample analysis from patients for pharmacokinetics research and medication monitoring.
Introduction
The Niraparib(Figure 1)Chemical name:((S)-2-(4-(piperidin-3-yl) phenyl)-2H-indazole-7-Carboxamide.Chemicalformula:C19H20N4Oand Molecular weight:320.396 g/mol[1].Niraparib(ZEJULA*) preferably blocks PARP 1&2 Enzymes [2-3].The primary cause of death from gynaecological cancer is ovarian cancer. Germ-line mutations in BRCA 1&2 have been found to be associated with an increased incidence ofboth familialovarian cancer & breast cancer. These genes are engaged in the processes that repair DNA damage.Enzymes in the PARP family are part of the base excision repair (BER) system. Synthetic lethality is associated with the use of PARP medicines in individuals with ovariancancer harboring a BRCA mutation[4-6]. It is an inhibitor of PARP-1&2, two polymerase enzymes involved in DNA repair. Studies conducted in-vitrohaveshown that Niraparibinduced cyto-toxicitymay be caused by decreased PARP activity as an enzyme and increased PARP-DNA complex formation, which results in DNA damage, necrosisand cell death [7-9]. Niraparibenhanced cyto-toxicityand decreased tumorgrowth in both mouse Xeno-graft models of human cancer cell lines with BRCA-1-1/2 defects and human patient-derived xenograft tumour models with homologous stem cells.[10-12].According to review of literature, only a few LC-MS/MSmethods for estimating Niraparibin rat & human plasmain integrated forms and individualhave been published [13–14].We found that the published techniques had numerous issues with stability and reproducibility for long-term analysis. The goal of the approach is to improve an analyte’s sensitivity in comparison to previously published methods, either as a single analyte or in combination with other analytes in various biological matrices. It also aims to have a short chromatographic run time of just over five minutes per sample, making the method applicable to high-throughput bioanalysis.
Nevertheless, analysts may find it challenging to completely understand the potential medications due to the complexities of clinical drug combinations. A patient’s medication history is frequently not fully documented, and the hospital medical records of 61% of patients contain one or more unregistered prescriptions. Combinations of drugs are also frequent. It would be difficult to find signal suppression by co-elution if the combination medication is co-eluted with the analytes in the biological analysis and is not included in the drug history.[15-20]The current study aims to develop and evaluate a bio-analytical method for LC-ESI-MS/MS-based Niraparibestimation in K3EDTA human plasma samples. According to US-FDA criteria, compare with the corresponding internal standard as deuterated Niraparib(Niraparib-D5) (Figure: 1). Additionally a straightforward extraction procedure that is extremely sensitive and linear with minimal plasma consumption needs to be devised.
MATERIALS AND METHODS
Chemicals and reagents
Niraparibstandard drug (STD), Niraparib-D5 internal standard (ISTD), Acetonitrile, Methanol, Ethyl-acetate (HPLC grade). Ammonium-formate, Ammonia Solutionand Ammonium-acetate (AR grade).Glacial-acetic acid (LR grade), Water (Milli-Q/HPLC grade).Human plasma having K3EDTA as an anti-coagulant. Other chemicals consumedfor this study were ARgradeand solvents were HPLC grade.